The goal of the proposed research is to increase our understanding of how the otolith organs improve retinal image stabilization by the vestibulo-ocular reflex (VOR). Semicircular canal and otolith signals are processed by vestibulo-ocular neurons and routed to the extraocular muscles to rotate the eyes in the direction opposite to head rotation. The vestibulo-ocular reflex thus maintains a constant direction of eyesight during head movement, which is necessary for clear vision. We will pursue three aims that examine the neuronal responses and pathways of otolith and canal signals of the VOR in cats, mice, and genetically altered mice. (1) Anatomy and neurochemistry of otolith and canal contributions to vestibulo-ocular reflex: Constant velocity rotations about non-vertical axes, in horizontal or vertical directions, will be used to excite head angular velocity estimation and expression of immediate early genes. Neurochemical markers will be co-localized with immediate early gene c-fos label in brainstem and cerebellum to classify neurons active or plastic during central nervous system estimation of head velocity. Anterograde/retrograde tracing combined with c-fos expression will relate cerebellar connections to activity or plasticity induced by velocity estimation. (2) Otolith and canal signals of vestibulo-ocular reflex neurons: The spike responses of vestibulo-ocular neurons will be recorded in awake animals during sinusoidal rotation, translation, and off-vertical axis rotations. Neurons that have connections with the cerebellar nodulus will be identified by electrical stimulation and compared to other brain stem vestibular neurons. We expect that signals related to central estimation of head angular velocity will be present selectively on neurons interconnected with nodulus. (3) Ablation of otolith and canal signals in cerebellum: We will make excitotoxic cerebellar lesions to test the role of the posterior vermis and fastigial deep nucleus in VOR of mice. The natural mutant mice pcd and stargazer will be used to examine the effects on the VOR of selective loss of cerebellar cortical output versus cerebellar cortical input. This research may help in understanding vision loss resulting from specific balance disorders.